Gene behind fatal brain disorder isolated

Washington: A blood test could help diagnose a devastating brain disorder that is often misdiagnosed and ends in fatality.

People who inherit the abnormal gene CSF1R always develop HDLS (hereditary diffuse leukoencephalopathy with spheroids), a disorder of the brain's white matter that leads to death between 40 and 60 years.

Mayo Clinic researchers in Florida have identified 14 different mutations in the gene CSF1R that bring on HDLS. Until now, a definite diagnosis required examination of brain tissue by biopsy or autopsy.

"Given this finding, we may soon have a blood test that can help doctors diagnose HDLS, and I predict we will find it is much more common than anyone could have imagined," says Mayo study investigator, neurologist Zbigniew K. Wszolek.

A number of people who tested positive for the abnormal gene had been diagnosed with a wide range of other conditions. They were related to a patient known to have HDLS, and so their genes were also examined, adds Wszolek.

"Because the symptoms of HDLS vary so widely, everything from behaviour and personality changes to seizures and movement problems, these patients were misdiagnosed as having either schizophrenia, epilepsy, Parkinson's, multiple sclerosis, stroke," says Wszolek.

"Many of these patients were therefore treated with drugs that offered only toxic side-effects," adds Wszolek. Wszolek's interest in HDLS began when a severely disabled young woman came to see him in 2003 and mentioned that other members of her family were affected.

The diagnosis of HDLS was made by his Mayo Clinic colleague, Dennis W. Dickson, who reviewed the autopsy findings of the patient's uncle, who had previously been misdiagnosed with multiple sclerosis, and subsequently, Wszolek's patient and her father. All members of the family had HDLS.

The study, which included 38 researchers from 12 institutions in five countries, led by Rosa Rademakers found the gene responsible for HDLS.